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Trial record 1 of 1 for:    04108156
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This Study Will Evaluate the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Participants With Diabetic Macular Edema Compared With Intravitreal Ranibizumab (Pagoda)

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ClinicalTrials.gov Identifier: NCT04108156
Recruitment Status : Active, not recruiting
First Posted : September 30, 2019
Last Update Posted : September 13, 2023
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Study Description
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Brief Summary:
This study will evaluate the efficacy, safety, and pharmacokinetics of the Port Delivery System with Ranibizumab (PDS) in Participants with Diabetic Macular Edema (DME) when treated every 24 weeks (Q24W) compared with intravitreal ranibizumab 0.5 mg every 4 weeks (Q4W).

Condition or disease Intervention/treatment Phase
Diabetic Macular Edema Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab Drug: Intravitreal Ranibizumab 0.5 mg Injection Phase 3

Study Design
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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 634 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Phase III, Multicenter, Randomized, Visual Assessor-Masked, Active-comparator Study of the Efficacy, Safety, and Pharmacokinetics of the Port Delivery System With Ranibizumab in Patients With Diabetic Macular Edema (Pagoda)
Actual Study Start Date : September 30, 2019
Actual Primary Completion Date : September 19, 2022
Estimated Study Completion Date : February 23, 2024

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Edema
Drug Information available for: Ranibizumab

Arms and Interventions
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Arm Intervention/treatment
Experimental: PDS Arm
Participants randomized to the PDS arm will receive intravitreal ranibizumab injection every 4 weeks (loading phase) and will then have the PDS implant (pre-filled with ranibizumab) surgically inserted. PDS implant refill-exchange procedures will be performed on a fixed interval every 24-weeks (Q24W) thereafter
 Drug: PDS Implant Pre-Filled with 100 mg/mL Ranibizumab
Will be administered as per the schedule described in individual arm.
Active Comparator: Intravitreal Arm
Participants randomized to the intravitreal arm will receive intravitreal ranibizumab injection every 4 weeks until they receive the PDS implant (pre-filled with ranibizumab). PDS implant refill-exchange procedures will be performed on a fixed interval Q24W thereafter.
 Drug: Intravitreal Ranibizumab 0.5 mg Injection
Will be administered as per the schedule described in individual arm.


Outcome Measures
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Primary Outcome Measures :
  1. Change in BCVA score from baseline averaged over Weeks 60 and 64 as measured using the ETDRS chart in the efficacy population using a treatment policy strategy for all intercurrent events [ Time Frame: Baseline to Week 64 ]

    BCVA = Best-Corrected Visual Acuity

    ETDRS = Early Treatment Diabetic Retinopathy Study

    A vision score of 20/20 vision is considered normal. A score of 20/200 is considered being legally blind.



Secondary Outcome Measures :
  1. Change in BCVA score from baseline averaged over Weeks 60 and 64 as measured with use of the ETDRS chart in the modified intent-to-treat (mITT) population using a treatment policy strategy for all intercurrent events [ Time Frame: Baseline to Week 64 ]
    ETDRS-DRSS = ETDRS Diabetic Retinopathy Severity Scale

  2. Change in BCVA score from baseline averaged over Weeks 60 and 64 as measured with use of the ETDRS chart in the mITT population using a hypothetical strategy for all intercurrent events [ Time Frame: Baseline to Week 64 ]
  3. Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 64 in the efficacy population [ Time Frame: Baseline to Week 64 ]
  4. Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS at Week 64 in the mITT population [ Time Frame: Baseline to Week 64 ]
  5. Change from baseline in BCVA as measured on the ETDRS chart over time [ Time Frame: Baseline up to Week 120 ]
  6. Percentage of participants who lose <15, <10, and <5 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 120 ]
  7. Percentage of participants who gain ≥15, ≥10, ≥5, ≥0 letters in BCVA from baseline over time [ Time Frame: Baseline up to Week 120 ]
  8. Percentage of participants with a BCVA Snellen equivalent of 20/40 or better over time [ Time Frame: Baseline up to Week 120 ]
  9. Percentage of participants with a BCVA Snellen equivalent of 20/200 or worse over time [ Time Frame: Baseline up to Week 120 ]
  10. Percentage of participants with a ≥2-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
  11. Percentage of participants with a ≥3-step improvement from baseline on the ETDRS-DRSS over time [ Time Frame: Baseline up to Week 120 ]
  12. Time to ≥2-step worsening from baseline on the ETDRS-DRSS [ Time Frame: Baseline up to Week 120 ]
  13. Time to ≥3-step worsening from baseline on the ETDRS-DRSS [ Time Frame: Baseline up to Week 120 ]
  14. Change from baseline in ETDRS-DRSS score over time [ Time Frame: Baseline up to Week 120 ]
  15. Change from baseline in CST as measured on SD-OCT over time [ Time Frame: Baseline up to Week 120 ]
  16. Change from baseline in total macular volume as measured on SD-OCT over time [ Time Frame: Baseline up to Week 120 ]
  17. Percentage of participants with absence of intraretinal fluid over time (intraretinal fluid as measured in the central 1 mm subfield) [ Time Frame: Baseline up to Week 120 ]
  18. Percentage of participants with absence of subretinal fluid over time (subretinal fluid as measured in the central 1 mm subfield) [ Time Frame: Baseline up to Week 120 ]
  19. Percentage of participants with absence of intraretinal fluid and subretinal fluid over time [ Time Frame: Baseline up to Week 120 ]
  20. Percentage of participants with absence DME (defined as CST ≥325 μm on SD-OCT) over time [ Time Frame: Baseline up to Week 120 ]
    DME = diabetic macular edema

  21. Time to PDR (defined as a score ≥60 on the ETDRS-DRSS) [ Time Frame: Baseline up to Week 120 ]
    PDR = proliferative diabetic retinopathy

  22. Percentage of participants who do not undergo supplemental treatment with intravitreal ranibizumab within each refill-exchange interval [ Time Frame: Baseline up to Week 120 ]
  23. Percentage of participants who report preferring PDS treatment compared with intravitreal ranibizumab treatment [ Time Frame: Baseline to Week 64 ]
    As measured by the PDS Patient Preference Questionnaire at Week 64 among patients in the PDS arm efficacy population, mITT population

  24. Percentage of participants who report preferring PDS treatment compared with intravitreal ranibizumab treatment, as measured by the PDS Patient Preference Questionnaire (PPPQ) at Week 64 [ Time Frame: Baseline to Week 64 ]
    Participants in in a subset of patients with bilateral disease who are simultaneously receiving ranibizumab via study eye PDS implant and fellow eye intravitreal injection

  25. Patient-reported vision-related functioning and health-related quality of life (HRQoL) among patients in both treatment arms, as measured by changes from baseline [ Time Frame: , Baseline Week 48, Week 96 ]
    As measured by in the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) composite score and Near Activities, Distance Activities, and Driving subscale scores

  26. Patient-reported vision-related functioning and HRQoL, as measured by the proportion of patients with a ≥ 4-point improvement from baseline in the NEI VFQ-25 composite score at Weeks 48 and 96 among patients in both treatment arms [ Time Frame: Baseline, Week 48, Week 96 ]
  27. Incidence and severity of ocular adverse events [ Time Frame: Baseline to Week 120 ]
  28. Incidence and severity of non-ocular adverse events [ Time Frame: Baseline up to Week 120 ]
  29. Incidence, severity, and duration of adverse events of special interest [ Time Frame: Baseline up to Week 120 ]
  30. Serum concentration of ranibizumab observed over time [ Time Frame: Baseline up to Week 120 ]
  31. PK parameter value area under the concentration- time curve over 24 weeks (AUC24W) [ Time Frame: Baseline to Week 24 ]
  32. Pharmacokinetic (PK) parameter maximum serum concentration (Cmax) [ Time Frame: Baseline up to Week 120 ]
  33. PK Parameter minimum serum concentration (Cmin) [ Time Frame: Baseline up to Week 120 ]
  34. Time of maximum observed serum concentration (Tmax) after PDS implant insertion [ Time Frame: Baseline up to Week 120 ]
  35. Prevalence of anti-drug antibodies (ADAs) at baseline and incidence of ADAs during the study [ Time Frame: Baseline up to Week 120 ]
  36. Prevalence of neutralizing antibodies at baseline and incidence of neutralizing antibodies during the study [ Time Frame: Baseline up to Week 120 ]
  37. Reported incidence of device deficiencies [ Time Frame: Baseline up to Week 120 ]
  38. Incidence and severity of ocular adverse events [ Time Frame: Baseline up to Week 120 ]
  39. Incidence, severity, and duration of ocular adverse events of special interest during the postoperative period (up to 37 days after initial implantation) and follow-up period (> 37 days after implantation surgery) [ Time Frame: Baseline up to Week 120 ]
  40. Incidence and severity of adverse device effects [ Time Frame: Baseline up to Week 120 ]
  41. Incidence, causality, severity, and duration of anticipated serious adverse device effects [ Time Frame: Baseline up to Week 120 ]

Eligibility Criteria
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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Age ≥18 years at time of signing Informed Consent Form
  • Documented diagnosis of diabetes mellitus (Type 1 or Type 2)
  • HbA1c level of ≤10% within 2 months prior to screening or at screening

Study eye

  • Macular thickening secondary to DME involving the center of the fovea with CST ≥325 um on SD-OCT at screening
  • BCVA score of 78 to 25 letters (20/32 to 20/320 approximate Snellen equivalent)

Exclusion Criteria:

  • High-risk proliferative diabetic retinopathy
  • Active intraocular inflammation (grade trace or above)
  • Suspected or active ocular or periocular infection of either eye
  • Uncontrolled ocular hypertension or glaucoma and any such condition the investigator determines may require a glaucoma-filtering surgery during a patient's participation in the study
  • Cerebrovascular accident or myocardial infarction within 6 months prior to randomization
  • Atrial fibrillation diagnosis or worsening within 6 months prior to randomization
  • Uncontrolled blood pressure
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04108156


Locations
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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
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Study Director: Clinical Trials Hoffmann-La Roche
More Information
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Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT04108156    
Other Study ID Numbers: GR40550
First Posted: September 30, 2019    Key Record Dates
Last Update Posted: September 13, 2023
Last Verified: September 2023
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: Qualified researchers may request access to individual patient level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm).

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hoffmann-La Roche:
Port Delivery System
Additional relevant MeSH terms:
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Macular Edema
Edema
Macular Degeneration
Retinal Degeneration
Retinal Diseases
Eye Diseases
Ranibizumab
 Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors
Antineoplastic Agents